The Clockwisdom of SMILES Part II

As many readers of this blog will be aware, a chiral SMILES is not a lopsided grin. Instead it is a way of describing the relative spatial arrangement of groups around a chiral centre using SMILES notation.

The following examples investigate this notation. The stereotypical examples are the following:

A. C[C@](Br)(Cl)I - ACW(C,Br,Cl,I)
B. C[C@H](Br)I    - ACW(C,H,Br,I)

where ACW(w,x,y,z) indicates anticlockwise in terms of x,y,z when looking from w. However, note that the first group does not necessarily need to appear before the chiral carbon:

C. [C@](C)(Br)(Cl)I - ACW(C,Br,Cl,I) (Same as A)
D. [C@H](C)(Br)I    - ACW(H,C,Br,I)  (Opposite of B)

What about ring closures? These are handled as followed:

E. C[C@H]1CCN1 -
ACW(C,H,N,C) (the 1 indicates a bond to the chiral C)
F. C[C@]12N(CC2)C1 -
ACW(C, the C1 carbon, the C2 carbon, N)
G. C[C@@]21N(CC2)C1 -
CW(C, the C2 carbon, the C1 carbon, N) (the same as F)

Note that ring closures directly before an atom do not indicate a bond to that atom. Try to draw the following and compare your result to that given by Daylight's Depict service:

H. [C@@]123[C@H](C(C=C3)(C)C)CC[C@@](C1)(CCC2)C

If you got that right, consider yourself a SMILES ninja.

Credit: Thanks to Craig James for his patient explanations.
Image credit: sean-b